High-dose cisplatin therapy using mannitol versus furosemide diuresis: comparative pharmacokinetics and toxicity.
The dose-limiting toxic effect of high-dose (100 mg/m2) cisplatin is renal insufficiency. Hydration with furosemide- or mannitol-induced diuresis has been reported to ameliorate this toxicity. Animal studies suggest that mannitol may be superior to furosemide in this regard. Twenty-two patients with advanced neoplasms refractory to conventional therapy were treated with cisplatin at a dose of 100 mg/m2 every 21--28 days. Patients were randomized to receive 37.5 g of mannitol by 6-hour infusion with cisplatin or 40 mg of furosemide prior to cisplatin therapy. Hydration with at least 1 liter of normal saline was given prior to cisplatin. Nephrotoxicity (creatinine greater than 2 mg/100 ml, creatinine clearance greater than 50 ml/minute) occurred in 19% of courses in the furosemide-treated group and in 28% of courses in the mannitol-treated group. Peak plasma platinum concentration, terminal half-life, urinary excretion, and percent protein-bound plasma platinum were similar in both groups. The use of cisplatin at this dose schedule resulted in similar toxicity and pharmacokinetics when using hydration with either furosemide or mannitol.
D000293:Adolescent; D000328:Adult; D000368:Aged; D002945:Cisplatin / Q000008:administration & dosage* / Q000378:metabolism; D004231:Diuresis; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology*; D007700:Kinetics; D008297:Male; D008353:Mannitol / Q000494:pharmacology*; D008875:Middle Aged; D011446:Prospective Studies
D008353:Mannitol; D005665:Furosemide; D002945:Cisplatin